Abstract
BackgroundIn Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. Intriguingly, the human orthologs of these proteins (MLL5, NCOR2, and TBL1X) are also important for the faithful completion of cytokinesis in tissue culture cells. Since MLL5, NCOR2, and TBL1X form a complex with the histone deacetylase, HDAC3, we sought to determine if an orthologous counterpart played a regulatory role in fission yeast cytokinesis.ResultsIn this report we identify the hos2 gene as the fission yeast HDAC3 ortholog. We show that Hos2p physically interacts with Set3p, Snt1p, and Hif2p, and that hos2∆ mutants are indeed compromised in their ability to reliably complete cell division in the presence of mild cytokinetic stresses. Furthermore, we demonstrate that over-expression of hos2 causes severe morphological and cytokinetic defects. Lastly, through recombinase mediated cassette exchange, we show that expression of human HDAC3 complements the cytokinetic defects exhibited by hos2∆ cells.ConclusionsThese data support a model in which Hos2p functions as an essential component of the Set3p-Snt1p-Hif2p complex with respect to the regulation of cytokinesis. The ability of human HDAC3 to complement the cytokinesis defects associated with the deletion of the hos2 gene suggests that further analysis of this system could provide insight into the role of HDAC3 in both the regulation of cell division, as well as other biological processes influenced by HDAC3 deacetylation.
Highlights
In Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress
Hos2p is required for the successful completion of cytokinesis in response to perturbation of the cell division machinery [20,21,22] To determine if an ortholog of HDAC3 existed in S. pombe, and if it too played a role in the regulation of cytokinesis, A BLAST search using human HDAC3 as query was performed
To determine if Hos2p played a role in cytokinesis, the hos2 gene deletion mutant was purchased from the commercial supplier, Bioneer
Summary
In Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. The SIN is composed of a GTPase signalling cascade that is essential for the temporal co-ordination of cytokinesis, ring constriction, and for the deposition of the division septum [3,5,9,10] In addition to these mechanisms, recent work has supported the existence of a cytokinesis monitoring system. This system has the capacity to generate a prolonged cytokinesis competent state (characterized by delayed entry into mitosis and the continuous repair/reestablishment of the actomyosin ring) that allows for the successful completion of cell division upon mild cytokinetic stresses [11,12,13,14,15,16,17]. In the absence of either Clp1p or Rad24p, cells are unable to maintain SIN signalling leading to cytokinesis failure and the generation of inviable, multinucleate cells [13,15,18]
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